Influence of simvastatin on bone regeneration of tibial defects and blood cholesterol level in rats

Abstract

The purpose of this study was to evaluate the effects of simvastatin, by oral or subcutaneous administration, on tibial defects regeneration and blood cholesterol level in rats. A surgical defect was made on the right tibia of 40 male animals assigned to 4 groups (n=10), based on two routes of administration and on the use or not of simvastatin: subcutaneous injection of simvastatin (7 mg/kg) (group AT) or only the vehicle of drug suspension (group AC), above the defect area, for 5 days; and 20 mg/kg of simvastatin macerated on water (group BT) or only water (group BC), orally, daily, during the whole observation period. The animals were sacrificed after 15 or 30 days, when blood samples were analyzed to check plasma cholesterol levels. Tibiae were removed and, after decalcification and routine laboratorial processing, histological and histomorphometrical analyses were carried out. ANOVA was used for statistical analysis at 5% significance level. The histological and histomorphometrical analyses showed significant differences only between the experimental periods (p<0.05). Animals sacrificed after 30 days showed better bone repair (p<0.05). There was no statistically significant difference (p>0.05) for blood cholesterol levels between the groups. In conclusion, simvastatin administration either orally or subcutaneously did not improve bone repair of experimental tibial defects and did not alter blood cholesterol levels in rats.

Three-Dimensional Porous Gelapin–Simvastatin Scaffolds Promoted Bone Defect Healing in Rabbits

“…Defects with length more than 2.5 times greater than diaphyseal TD would not heal spontaneously [2]. We also selected 30 and 60 day time points because in an effective bone healing, the hard callus forms after 4-6 weeks, while the bone healing continues by remodeling after eight to several weeks [12,29,30]. After insertion of the Gel-Sim scaffolds in LRBDs, the modulatory roles of Sim on inflammation, particularly the macrophages, resulted in a proper reparative phase to occur.…”

“…In a study in rats, it has been shown that Sim administration either orally (20 mg/kg) or subcutaneously (7 mg/kg) did not improve bone repair of experimental tibial defects [30]. Alternatively, direct injection of Sim in rat bony defect for three consecutive days improved new bone formation; however, the effect did not continue when the administration was terminated [29].…”

Rosuvastatin Promotes Osteoblast Differentiation and Regulates SLCO1A1 Transporter Gene Expression in MC3T3-E1 Cells

“…However, in appropriate doses, statins may have therapeutic applications for the treatment of osteoporosis. In fact, several studies have demonstrated positive effects on bone when statins are administered orally [7,22,34], subcutaneously [7,9,35,36] or locally to bone sites [37][38][39][40][41][42][43][44]. Nevertheless, the route of administration and dosage form of statins still has to be optimized to maximize their efficacy in bone.…”

The influence of local administration of simvastatin in calvarial bone healing in rats

“…This has prompted other investigators to study the effects of locally applied statins. Some authors findings have demonstrated the anabolic effects of statins on bone repair (Wong and Rabie, 2003;Kiliçcoglu and Erdemli, 2007;Nyan et al, 2007;Wang et al, 2007;Wu et al, 2007;Jeon et al, 2008;Lee et al, 2008), while others did not find any beneficial effects (Anbinder et al, 2006;Kiliç et al, 2008;Ma et al, 2008). Optimal doses and carriers have not yet been defined, and the subject is still controversial.…”